Nhi Thi Hong Nguyen

Renin-Angiotensin-Aldosterone System Inhibitors and Development of Gynecologic Cancers: A 23 Million Individual Population-Based Study

The chronic receipt of renin-angiotensin-aldosterone system (RAAS) inhibitors including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been assumed to be associated with a significant decrease in overall gynecologic cancer risks. This study aimed to investigate the associations of long-term RAAS inhibitors use with gynecologic cancer risks. A large population-based case-control study was conducted from claim databases of Taiwan’s Health and Welfare Data Science Center (2000–2016) and linked with Taiwan Cancer Registry (1979–2016). Each eligible case was matched with four controls using propensity matching score method for age, sex, month, and year of diagnosis. We applied conditional logistic regression with 95% confidence intervals to identify the associations of RAAS inhibitors use with gynecologic cancer risks. The statistical significance threshold was p < 0.05. A total of 97,736 gynecologic cancer cases were identified and matched with 390,944 controls. The adjusted odds ratio for RAAS inhibitors use and overall gynecologic cancer was 0.87 (95% CI: 0.85–0.89). Cervical cancer risk was found to be significantly decreased in the groups aged 20–39 years (aOR: 0.70, 95% CI: 0.58–0.85), 40–64 years (aOR: 0.77, 95% CI: 0.74–0.81), ≥65 years (aOR: 0.87, 95% CI: 0.83–0.91), and overall (aOR: 0.81, 95% CI: 0.79–0.84). Ovarian cancer risk was significantly lower in the groups aged 40–64 years (aOR: 0.76, 95% CI: 0.69–0.82), ≥65 years (aOR: 0.83, 95% CI: 0.75–092), and overall (aOR: 0.79, 95% CI: 0.74–0.84). However, a significantly increased endometrial cancer risk was observed in users aged 20–39 years (aOR: 2.54, 95% CI: 1.79–3.61), 40–64 years (aOR: 1.08, 95% CI: 1.02–1.14), and overall (aOR: 1.06, 95% CI: 1.01–1.11). There were significantly reduced risks of gynecologic cancers with ACEIs users in the groups aged 40–64 years (aOR: 0.88, 95% CI: 0.84–0.91), ≥65 years (aOR: 0.87, 95% CI: 0.83–0.90), and overall (aOR: 0.88, 95% CI: 0.85–0.80), and ARBs users aged 40-64 years (aOR: 0.91, 95% CI: 0.86–0.95). Our case-control study demonstrated that RAAS inhibitors use was associated with a significant decrease in overall gynecologic cancer risks. RAAS inhibitors exposure had lower associations with cervical and ovarian cancer risks, and increased endometrial cancer risk. ACEIs/ARBs use was found to have a preventive effect against gynecologic cancers. Future clinical research is needed to establish causality.

The Potential Impact of Histamine-2 Receptor Antagonists on Gynecologic Cancer Risk: A Population-Based Study of 23 Million Individuals

Abstract Background: Gynecologic cancers, including cervical, endometrial, and ovarian cancers, remain a major global health burden. Although histamine-2 receptor antagonists (H2RA) are inexpensive and widely accessible agents with reported anticancer properties, their associations with gynecologic cancer risk remain unclear. This study evaluated the potential of H2RAs for repurposing in chemoprevention. Methods: A nationwide, population-based case–control study was conducted using Taiwan’s National Health Insurance claims and Cancer Registry data from 2002 to 2016. A total of 97,736 women with newly diagnosed gynecologic cancer were matched 1:4 with controls by sex, age (±5 years), and month and year of diagnosis. H2RA exposure was defined as >60 days of use within two years before the index date. Adjusted odds ratios (aOR) and 95% confidence intervals were estimated using conditional logistic regression, adjusting for age, Charlson comorbidity index, and use of metformin, aspirin, and statins. Results: H2RA use was associated with reduced risks of cervical (aOR 0.80), endometrial (0.68), and ovarian cancers (0.78). Age-stratified analyses showed lower risks of cervical and endometrial cancers across all age groups, whereas the reduced ovarian cancer risk was most evident in women aged 40 to 64. Individual H2RA agents showed protective effects in the overall population, with cimetidine demonstrating the broadest reduction. Conclusions: Long-term H2RA use was associated with lower risks of major gynecologic cancers, with notable age- and agent-specific differences. Prospective studies are warranted to confirm causality and inform clinical application. Impact: Findings support repurposing H2RAs as accessible chemopreventive candidates for further translational application in women.